The ABC transporter AtrB from Aspergillus nidulans mediates resistance to all major classes of fungicides and some natural toxic compounds
The ABC transporter AtrB from Aspergillus nidulans mediates resistance to all major classes of fungicides and some natural toxic compounds
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DOI：
10.1099/00221287-146-8-1987
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发表时间：
2000-08-01
期刊：
影响因子：
2.8
通讯作者：
De Waard, MA
中科院分区：
文献类型：
--
作者：
Andrade, AC;Del Sorbo, G;De Waard, MA
本文报道了构巢曲霉ABC转运蛋白AtrBp的功能特性。AtrBp是一种多药物转运蛋白，对所有主要类别的农业杀真菌剂和一些天然有毒化合物的底物具有亲和力。通过评估atrB的缺失和过表达突变体对几种毒物的敏感性来确定AtrBp的底物谱。与对照分离株相比，所有突变株均显示正常生长。Δ atrB突变体对苯胺基嘧啶、苯并咪唑、苯基吡咯、苯基吡啶胺、strobirulin和一些唑类杀菌剂的敏感性增加。对天然有毒化合物喜树碱（生物碱）、植物抗毒素白藜芦醇（芪）和诱变剂4-硝基喹啉氧化物的敏感性增加也被发现。除了上述化合物外，还观察到对更广泛范围的唑类、二甲酰亚胺类、五氯硝基苯、乙酰黄烷和罗丹明6 G的敏感性降低。过表达突变体的敏感性降低与atrB表达水平呈负相关。有趣的是，过表达突变体显示出对二硫代氨基甲酸盐杀真菌剂、百菌清和铁活化抗生素腐草霉素的敏感性增加。与亲本分离物相比，过表达突变体对唑类杀真菌剂[（14）C]fenarimol的积累较低，表明AtrBp通过防止毒物的细胞内积累起作用。各种代谢抑制剂将过表达突变体中[（14）C]fenarimol的积累水平增加到野生型水平，表明这些突变体中杀真菌剂的积累减少是由于AtrBp的较高泵容量导致的能量依赖性流出增加。
This paper reports the functional characterization of AtrBp, an ABC transporter from Aspergillus nidulans. AtrBp is a multidrug transporter and has affinity to substrates belonging to all major classes of agricultural fungicides and some natural toxic compounds. The substrate profile of AtrBp was determined by assessing the sensitivity of deletion and overexpression mutants of atrB to several toxicants. All mutants showed normal growth as compared to control isolates. Delta atrB mutants displayed increased sensitivity to anilinopyrimidine, benzimidazole, phenylpyrrole, phenylpyridylamine, strobirulin and some azole fungicides. Increased sensitivity to the natural toxic compounds camptothecin (alkaloid), the phytoalexin resveratrol (stilbene) and the mutagen 4-nitroquinoline oxide was also found. Overexpression mutants were less sensitive to a wide range of chemicals. In addition to the compounds mentioned above, decreased sensitivity to a broader range of azoles, dicarboximides, quintozene, acriflavine and rhodamine 6G was observed. Decreased sensitivity in overexpression mutants negatively correlated with levels of atrB expression. Interestingly, the overexpression mutants displayed increased sensitivity to dithiocarbamate fungicides, chlorothalonil and the iron-activated antibiotic phleomycin. Accumulation of the azole fungicide [(14)C]fenarimol by the overexpression mutants was lower as compared to the parental isolate, demonstrating that AtrBp acts by preventing intracellular accumulation of the toxicant. Various metabolic inhibitors increased accumulation levels of [(14)C]fenarimol in the overexpression mutants to wildtype levels, indicating that reduced accumulation of the fungicide in these mutants is due to increased energy-dependent efflux as a result of higher pump capacity of AtrBp.